The goal is to develop new automated morphometric techniques to establish criteria for the identification of atypical (premalignant) epithelial cells in sputum. Analysis of bronchial squamous metaplasia and cellular-atypias is done by quantitatively analyzing 200 such cells by color and density, reducing cell images to specific numerical values that quantify the degree of atypia, and analyzing the distribution of atypical cells in different cytological specimens from the same individual. Studies will compare smokers with nonsmokers, smokers with and without lung cancer, and subjects occupationally exposed to asbestos, uranium, and smoke. For each subject, sputum specimens suitable for image analysis will be prepared, visually selected cells scanned by a computer-controlled microscope, and the data transferred to a second computer for conversion to a numerical description of cell morphology. Electro-optical data-digitizing techniques and computerized cell image analysis procedures have been developed. A newly implemented nuclear boundary (N/C ratio) algorithm has been used to generate features that require exact specification of the nuclear boundary and the location of the nucleus. A comprehensive automated system for cell image analysis has been assembled. Its research and support capabilities include the generation of 271 features per cell. Visual atypical cell profiles indicate that the relative frequency of occurrence of atypical cells in the various classes compares favorably with the atypical cell profiles predicted by Atypia Status Index algorithm. Preliminary data indicate that the premalignant atypical bronchial epithelial cells in sputum progress in a stepwise fashion from squamous metaplasia through mild, moderate, and severe atypia to squamous carcinoma, with moderate atypia being the significant breakpoint. (3)